Anticaries compositions

ABSTRACT

Compositions providing improved protection against dental caries consisting of a pharmaceutically acceptable fluoride compound and a pharmaceutically acceptable poly(vinylbenzoic acid) in a suitable vehicle are described.

BACKGROUND OF THE INVENTION

The present invention relates to compositions for preventing dentalcaries. More particularly, it relates to fluoride-containingcompositions that have enhanced activity in preventing dental caries.

The use of soluble fluoride salts, such as stannous fluoride and sodiumfluoride, to reduce the incidence of dental caries in the generalpopulation is a well-known and ongoing endeavor. The administration ofthese fluoride compounds takes many forms, including the fluoridation ofdrinking water, professional treatment by dentists and incorporation inoral hygiene compositions such as dentifrices and mouthrinses.

Notwithstanding the widespread acceptance of such compositions, there isan ongoing search for more effective compositions and, therefore, thereis a need to enhance the fluoride activity of various fluoride compoundsby the addition of other compounds. In copending U.S. patent applicationSer. No. 303,284, filed Sept. 17, 1981 now U.S. Pat. No. 4,396,599,there is suggested the use of various zinc salts to enhance the activityof fluoride compounds.

One of the objects of the present invention is to provide improvedcompositions for preventing dental caries.

Another object of this invention is to provide anticaries compositionscomprising one or more anticaries compounds in combination with acompound which enhances the anticaries activity of said anticariescompounds. These and other objects of the invention will become apparentfrom the foregoing description.

SUMMARY OF THE INVENTION

In accordance with the present invention, there are providedcompositions useful in preventing dental caries comprising (a) at leastone fluoride salt and (b) a specific metal salt of poly(vinylbenzoicacid).

The enhancing effect on the anticaries properties of the compositions ofthe present invention is most notable when the fluoride salt is employedwith the metal salt of poly(vinylbenzoic acid) within specificconcentrations and the compositions of the invention can be employed invarious oral hygiene products.

DETAILED DESCRIPTION OF THE INVENTION

It has now been discovered that the rate of development of dentalcaries, as characterized by proximal, smooth surface, pit and fissurecaries, can be prevented or substantially retarded by the dailyapplication to the teeth of a composition comprising a pharmaceuticallyacceptable oral hygiene vehicle containing an effective concentration toprevent or inhibit dental caries of a pharmaceutically acceptablefluoride salt and a pharmaceutically acceptable metal salt ofpoly(vinylbenzoic acid).

Typical pharmaceutically acceptable fluoride compounds that are suitablefor use in the compositions of this invention include sodium fluoride,potassium fluoride, lithium fluoride, aluminum fluoride, zinc fluoride,stannous fluoride, sodium monofluorophosphate, acidulated phosphatefluoride, ammonium fluoride, ammonium bifluoride and amine fluoride.

The metal salts of poly(vinylbenzoic acid) found useful in accordancewith the present invention are essentially metal salts of thehomopolymers of vinylbenzoic acid, wherein the repeating unit of thepolymer is represented by structure (A), ##STR1## where M is selectedfrom the group consisting of sodium, potassium, lithium, calcium,aluminum, copper, magnesium, ammonium and substituted ammonium ionsderived from pharmaceutically acceptable organic amines.

The poly(vinylbenzoic acid) polymers required as intermediates for thepreparation of the salts of structure (A) are readily prepared by thefree radical polymerization of vinylbenzoic acid monomers, typified bythe 4-vinylbenzoic acid available from Pfaltz and Bauer. Neutralizationof the poly(vinylbenzoic acid) polymers with alkali metal hydroxides, oraddition of at least stoichiometric quantities of an alkali metal oxide,carbonate, chloride, nitrate, acetate, or sulfate, suffices to producethe polymeric salts of this invention. If desired, the aqueous solutionsof the polymeric salts can be purified by dialysis and the dialyzedpolymer solution freeze-dried, spray-dried, or evaporated to afford thepolymeric salts in the solid form.

In connection with the above compositions, the fluoride ionconcentration should be from about 0.005 to 2.00% by weight of the totalcomposition, preferably from about 0.01 to 1.00%. The concentration ofthe poly(vinylbenzoic acid) should be at least 0.0001% by weight of thetotal composition, preferably from about 0.01 to 5.00% and mostpreferably from about 0.05 to 3.00%. In concentrate formulations, thepoly(vinylbenzoic acid) may have a concentration as high as 80% byweight of the total composition.

Suitable pharmaceutically acceptable oral hygiene vehicles, that may beused alone or in any compatible combination, include glycerol, water,ethanol, polyethylene glycol, propylene glycol and sorbitol.Alternatively, any pharmaceutically acceptable vehicle which iscompatible with the poly(vinylbenzoic acid) and fluoride salts used maybe employed.

The compositions of this invention may be in the form of a mouthrinse,dentifrice, gel, powder, solution, varnish, lozenge, chewing gum, slowrelease device or concentrate to be diluted or other form suitable fororal application. Any pharmaceutically acceptable materials, such asthose ordinarily used in such oral compositions, that are compatible maybe employed in the compositions of this invention.

In accordance with the present invention, the compositions are appliedto the teeth with an appliance, e.g., toothbrush, swab, mechanicalcleansing devices, impregnated dental floss or the like, by gentlybrushing the teeth at least once daily, more preferably twice daily.

Specific embodiments of the anticaries compositions prepared inaccordance with the present invention are illustrated by the followingrepresentative examples. It will be understood, however, that theinvention is not confined to the specific limitations set forth in theindividual examples, but rather to the scope of the appended claims.

EXAMPLE I

A gel dentifrice is prepared as follows: the Pluronic F-127 surfaceactive agent is dissolved in 50 ml. of deionized water with continuousstirring at 70° C. The sodium poly(4-vinylbenzoate) is then added withstirring until dissolved. The resultant solution is then cooled to 50°C. and the sodium fluoride, glycerol, sorbitol, sodium benzoate,sweetener, flavoring, dye and silicone dioxide are individually added.The pH of the solution is then adjusted to 5.5 to 6.0 with 1.0N HCl or1.0N NaOH as required and deionized water is added to bring the totalweight to 100 g. The solution is permitted to gel overnight at 15° C.

The resulting gel dentifrice has the following composition:

    ______________________________________                                                               % w/w                                                  ______________________________________                                        sodium fluoride          0.22                                                 sodium poly (4-vinylbenzoate)                                                                          1.00                                                 silicon dioxide          1.00                                                 Pluronic F-127 (Wyandotte Chemicals Cor-                                                               18.00                                                poration's tradename for a nonionic sur-                                      face active agent prepared by the addition                                    of ethylene oxide to polypropylene glycol)                                    sweetener                0.80                                                 sodium benzoate          0.30                                                 glycerol                 10.00                                                sorbitol solution, 70%   2.00                                                 flavoring                0.80                                                 dye (0.5% aq. soln.)     0.70                                                 deionized water          q.s. to 100                                          ______________________________________                                    

EXAMPLE II

An abrasive paste dentifrice is prepared as follows: the sodiumfluoride, sodium benzoate, sweetener, Pluronic F87 and sodiumpoly(4-vinylbenzoate) are dissolved in 25 ml. of water at 50° C. withcontinuous stirring. In separate vessels, the xanthan gum is mixed withthe glycerol and the Natrosol 250H is mixed with the sorbitol and theneach of these mixtures is added to the solution. The Zeothix 265,titanium dioxide, and hydrous silica gel are then individually added tothe solution with stirring. The pH of the solution is then adjusted to5.0 to 6.0 with 1.0N HCl or 1.0N NaOH as required and the flavoring isthen added as well as enough deionized water to bring the solution to100 g. The resultant product is mixed and placed in containers andpermitted to stand at 20° C. overnight.

The resulting abrasive paste dentifrice has the following composition:

    ______________________________________                                                                % w/w                                                 ______________________________________                                        sodium fluoride           0.22                                                sodium poly(4-vinylbenzoate)                                                                            1.00                                                sodium benzoate           0.20                                                sweetener                 0.50                                                titanium dioxide          0.50                                                flavoring                 1.00                                                glycerol                  10.00                                               sorbitol soln. 70%        12.00                                               hydrous silica gel        15.00                                               Zeothix 265               9.00                                                Natrosol 250H (Hercules Inc. tradename for                                                              1.00                                                nonionic water soluble cellulose ether)                                       xanthan gum               1.00                                                Pluronic F87 (Wyandotte Chemical Corporation's                                                          3.00                                                tradename for a nonionic surface active agent                                 prepared by the addition of ethylene oxide to                                 polypropylene glycol)                                                         deionized water           q.s. to 100                                         ______________________________________                                    

EXAMPLE III

A mouthrinse solution is prepared as follows: the flavoring is dissolvedin ethanol in a suitable stainless steel vessel. The Pluronic F-108,water, glycol, sorbitol, sweetener, copper poly(4-vinylbenzoate) andsodium fluoride are individually added with continuous stirring. The pHis adjusted to 5.5 to 6.0 with 1.0N HCl and the entire solution isstrained through a 400 mesh stainless steel screen.

The resulting mouthrinse has the following composition:

    ______________________________________                                                                % w/w                                                 ______________________________________                                        sodium fluoride           0.05                                                copper poly(4-vinylbenzoate)                                                                            0.02                                                ethanol, USP              7.0                                                 Pluronic F108 (Wyandotte Chemical Corporation's                                                         2.00                                                tradename for a nonionic surface active agent                                 prepared by the addition of ethylene oxide to                                 polypropylene glycol)                                                         glycerol                  10.00                                               sorbitol soln. 70%        10.00                                               sweetener                 0.20                                                flavoring                 0.20                                                deionized water           q.s. to 100                                         ______________________________________                                    

EXAMPLE IV

An in vitro assay technique is utilized to demonstrate the enhancingproperties of the poly(vinylbenzoic acid) on fluoride ion activity. Thistechnique is based on the titrametric measurement of organic acidsproduced from sucrose by the cariogenic bacterium S. mutans.

A fresh cell suspension of Streptococcus mutans 6715, grown inTrypticase Soy Broth for 16-18 hrs. at 35° C., centrifuged and the cellsthen resuspended in buffer containing dithiothreitol is used in theassay system. The cell suspension is stored under anaerobic conditionsat 4° C. until used. The assay utilizes a pH-stat and the reaction iscarried out under a nitrogen atmosphere at 37° C. The production of acidis monitored with the automatic addition of 0.005N potassium hydroxidesolution. The cells are initially activated with glucose at pH 7.5.After the exhaustion of glucose, the pH of the reaction mixture ismanually dropped to 5.5 with 0.1N HCl. Sucrose is added and after 4minutes of acid production, the test compound is added. The rate of acidproduction is recorded as ml of potassium hydroxide consumed per minuteto maintain a pH of 5.5. Antiacidogenic activity is reported as thatamount of compound which reduces the acid production by a given percentas compared to a control containing no test compound. The higher thepercent reduction of acid production of a composition containing thealkali metal salt of poly(vinylbenzoic acid) and fluoride ion comparedto a composition containing the poly(vinylbenzoic acid) alone, thebetter the anticaries activity of such a composition. When sodiumpoly(4-vinylbenzoate) is tested as above, the following results areobtained:

    ______________________________________                                        % reduction of acid production                                                fluoride alone                                                                          compound alone                                                                             compound plus fluoride ion                             ______________________________________                                        20        0            31                                                     ______________________________________                                    

In addition to the preferred embodiments described herein, otherembodiments, arrangements, and variations within the spirit of theinvention and the scope of the appended claims will occur to thoseskilled in the art.

What is claimed is:
 1. In a composition for preventing dental cariesconsisting essentially of a pharmaceutically acceptable oral hygienevehicle containing an effective concentration to prevent caries of atleast one pharmaceutically acceptable fluoride salt; the improvementwhich consists of including therewith a fluoride ion activatingenhancing amount of a metal salt of poly(vinylbenzoic acid) havingrepeating units of structure (A), ##STR2## wherein M is selected fromthe group consisting of lithium, sodium, potassium, calcium, magnesium,aluminum, copper, ammonium and substituted ammonium ions derived frompharmaceutically acceptable organic amines.
 2. The composition of claim1 wherein the metal salt of poly(vinylbenzoic acid) is sodiumpoly(4-vinylbenzoic acid).
 3. The composition of claim 1 wherein themetal salt of poly(vinylbenzoic acid) is copper poly(4-vinylbenzoate).4. The composition of claim 1 wherein said fluoride salt is selectedfrom the group consisting of sodium fluoride, potassium fluoride,lithium fluoride, aluminum fluoride, zinc fluoride, stannous fluoride,sodium monofluorophosphate, acidulated phosphate fluoride, ammoniumfluoride, ammonium bifluoride and amine fluoride.
 5. The composition ofclaim 1 wherein the fluoride ion is present in a concentration of fromabout 0.005 to 2.00% by weight of the total composition.
 6. Thecomposition of claim 1 wherein the metal salt of poly(vinylbenzoic acid)is present in an amount of from about 0.0001 to 80.00% by weight of thetotal composition.